Fibronectin (Fn) is a 55OkDa glycoprotein found in most body fluids and in fibrillar form in most tissues where it mediates adhesion, spreading and migration of many cell types. It plays a major role in embryogenesis, cancer, wound healing, tissue remodeling, hematopoiesis, blood coagulation and fibrinolysis. Fn also facilitates removal of damaged tissue and clot remnants from circulation by phagocytes. Many bacteria and parasites are thought to use Fn as a means of colonizing tissue. Fn is a "mosaic" protein composed of homologous modules (domains) of three different types that are also found in other proteins. The long range goal of this research is to understand the structure and function of each module in Fn, to know which ones are involved in the multiplicity of interactions and which amino acids within those modules participate directly in the recognition process. This will be accomplished by isolating ever smaller fragments by classical or recombinant techniques, characterizing their interactions and folding properties by calorimetry and fluorescence, and determining as much as possible about their structure.This application emphasizes the self- interactions that govern the supertertiary structure of Fn in solution and its transformation into an insoluble fibrillar component of the extracellular matrix. In addition we wish to continue our characterization of hetero-interactions with selected macromolecules (collagen, fibrinogen, heparin, S.aureus peptides) and to collaborate with others to elucidate the 3D structure of various fragments. The knowledge gained will provide a better understanding of the many functions of Fn and may suggest improved methods of intervention in disease processes.